Background Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown. Objective To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance. Design Randomized, 2-period, 2-condition, crossover clinical study. Setting University of Chicago Clinical Resource Center. Participants Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m2 (SD, 1.6). Intervention Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity. Measurements Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt–tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test. Results The insulin concentration for the half-maximal pAkt–tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt–tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity. Limitation This was a single-center study with a small sample size. Conclusion Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues. Primary Funding Source National Institutes of Health.

Aims/hypothesis Sleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels. Methods We studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test. Results Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels. Conclusions/interpretation Sleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss.

Objective Sleep curtailment has been linked to obesity, but underlying mechanisms remain to be elucidated. We assessed whether sleep restriction alters 24-hour profiles of appetite-regulating hormones ghrelin, leptin and pancreatic polypeptide during a standardized diet, and whether these hormonal alterations predict food intake during ad libitum feeding. Methods Nineteen healthy, lean men were studied under normal sleep and sleep restriction in a randomized crossover design. Blood samples were collected for 24-hours during standardized meals. Subsequently, participants had an ad libitum feeding opportunity (buffet meals and snacks) and caloric intake was measured. Results Ghrelin levels were increased after sleep restriction as compared to normal sleep (p<0.01). Overall, sleep restriction did not alter leptin or pancreatic polypeptide profiles. Sleep restriction was associated with an increase in total calories from snacks by 328 ± 140 Kcal (p=0.03), primarily from carbohydrates (p=0.02). The increase in evening ghrelin during sleep restriction was correlated with higher consumption of calories from sweets (r=0.48, p=0.04). Conclusions Sleep restriction as compared to normal sleep significantly increases ghrelin levels. The increase in ghrelin is associated with more consumption of calories. Elevated ghrelin may be a mechanism by which sleep loss leads to increased food intake and the development of obesity.

Purpose of review To summarize recent developments linking disturbances of sleep and circadian rhythms to an increased risk for obesity, and to review novel research on potential countermeasures. Recent findings Effective treatments for obesity are limited, with long-term adherence to life style changes proving difficult. Identifying new preventive strategies based on modifiable risk factors is therefore imperative in the fight against obesity. Disturbances of sleep and circadian rhythms have an adverse impact on food choices, hunger and appetite and have lifelong deleterious metabolic effects when present during childhood and early adulthood. The upregulation of the endocannabinoid system and abnormalities in the temporal distribution of caloric intake have been recently implicated in the link between sleep loss and obesity risk. Lastly, alterations in the circadian variation in the composition and functionality of the gut microbiome have been identified as potential contributors to metabolic dysfunction in conditions of jet lag and shift work. Insufficient sleep and circadian misalignment are thus new modifiable risk factors for obesity. Emerging evidence suggests that novel countermeasures, such as manipulations of the timing of food intake, may be effective strategies in the prevention of obesity. Summary Four important findings are briefly reviewed: 1. disturbances of sleep and circadian rhythms in children and young adults are risk factors for the development of lifelong obesity; 2. circadian misalignment, as occurs in shift work, has an adverse impact on energy balance and increases the risk of weight gain; 3. the endocannabinoid system, an important regulator of hedonic feeding, could be a potential link between sleep, circadian rhythms and feeding behavior; 4. disturbances of the circadian variation in composition of the gut microbiome could be involved in the increased risk of obesity associated with insufficient sleep and circadian misalignment.

OBJECTIVETo assess whether the presence of obstructive sleep apnea (OSA) affects glucose metabolism in young, lean individuals who are healthy and free of cardiometabolic disease.RESEARCH DESIGN AND METHODSIn a prospective design, 52 healthy men (age 18–30 years; BMI 18–25 kg/m2) underwent laboratory polysomnogram followed by a morning oral glucose tolerance test (OGTT). We stratified all subjects according to the presence or absence of ethnicity-based diabetes risk and family history of diabetes. We then used a frequency-matching approach and randomly selected individuals without OSA, yielding a total of 20 control men without OSA and 12 men with OSA. Indices of glucose tolerance, insulin sensitivity, and insulin secretion (early phase and total) were compared between men with OSA and control subjects. The incremental areas under the glucose (incAUCglu) and insulin (incAUCins) curves were calculated using the trapezoidal method from 0 to 120 min during the OGTT.RESULTSMen with OSA and control subjects were similar in terms of age, BMI, ethnicity-based diabetes risk, family history of diabetes, and level of exercise. Both groups had normal systolic and diastolic blood pressure and fasting lipid levels. After ingestion of a glucose load, men with OSA had 27% lower insulin sensitivity (estimated by Matsuda index) and 37% higher total insulin secretion (incAUCins) than the control subjects, despite comparable glucose levels (incAUCglu).CONCLUSIONSIn young, lean, and healthy men who are free of cardiometabolic disease, the presence of OSA is associated with insulin resistance and a compensatory rise in insulin secretion to maintain normal glucose tolerance. Thus, OSA may increase the risk of type 2 diabetes independently of traditional cardiometabolic risk factors.

BackgroundThe last 50–100 years has been marked by a sharp rise in so-called “Western-diseases” in those countries that have experienced major industrial advances and shifts towards urbanized living. These diseases include obesity, type 2 diabetes, inflammatory bowel diseases, and food allergies in which chronic dysregulation of metabolic and/or immune processes appear to be involved, and are likely a byproduct of new environmental influences on our ancient genome. What we now appreciate is that this genome consists of both human and co-evolved microbial genes of the trillions of microbes residing in our body. Together, host–microbe interactions may be determined by the changing diets and behaviors of the Western lifestyle, influencing the etiopathogenesis of “new-age” diseases.Scope of reviewThis review takes an anthropological approach to the potential interplay of the host and its gut microbiome in the post-industrialization rise in chronic inflammatory and metabolic diseases. The discussion highlights both the changes in diet and the physical environment that have co-occurred with these diseases and the latest evidence demonstrating the role of host–microbe interactions in understanding biological responses to the changing environment.Major conclusionsTechnological advances that have led to changes in agriculture and engineering have altered our eating and living behaviors in ways never before possible in human history. These changes also have altered the bacterial communities within the human body in ways that are seemingly linked with the rise of many intestinal and systemic metabolic and inflammatory diseases. Insights into the mechanisms of this reciprocal exchange between the environment and the human gut microbiome may offer potential to attenuate the chronic health conditions that derail quality of life. This article is part of a special issue on microbiota.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host–gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.

Traditional risk factors for obesity and the metabolic syndrome, such as excess energy intake and lack of physical activity, cannot fully explain the high prevalence of these conditions. Insufficient sleep and circadian misalignment predispose individuals to poor metabolic health and promote weight gain and have received increased research attention in the past 10 years. Insufficient sleep is defined as sleeping less than recommended for health benefits, whereas circadian misalignment is defined as wakefulness and food intake occurring when the internal circadian system is promoting sleep. This Review discusses the impact of insufficient sleep and circadian misalignment in humans on appetite hormones (focusing on ghrelin, leptin and peptide-YY), energy expenditure, food intake and choice, and risk of obesity. Some potential strategies to reduce the adverse effects of sleep disruption on metabolic health are provided and future research priorities are highlighted. Millions of individuals worldwide do not obtain sufficient sleep for healthy metabolic functions. Furthermore, modern working patterns, lifestyles and technologies are often not conducive to adequate sleep at times when the internal physiological clock is promoting it (for example, late-night screen time, shift work and nocturnal social activities). Efforts are needed to highlight the importance of optimal sleep and circadian health in the maintenance of metabolic health and body weight regulation.